December 18, 2009 -
This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the Adobe-Forms-B version of the application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the Adobe-Forms-A version of the application forms and instructions.

October 9, 2009 - See Notice NOT-DA-10-001 Notification that NIDA is
Seeking Research Proposals Addressing the Clinical, Population and
Societal Impact of the Family Smoking Prevention and Tobacco Control Act
(H.R. 1256).

Program
Announcement (PA) Number: PA-08-125

NOTICE: Applications submitted in response
to this Funding Opportunity Announcement (FOA) for Federal assistance must be
submitted electronically through Grants.gov (http://www.grants.gov)
using the SF424 Research and Related (R&R) forms and the SF424 (R&R)
Application Guide.

APPLICATIONS
MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA
must be read in conjunction with the application guidelines included with this
announcement in Grants.gov/Apply
for Grants (hereafter called Grants.gov/Apply).

A
registration process is necessary before submission and applicants are highly
encouraged to start the process at least four (4) weeks prior to the grant
submission date. See Section IV.

Purpose: This
funding opportunity announcement (FOA) encourages
exploratory/developmental research projects to expand the application of
drug abuse epidemiologic research focused on understanding the nature,
extent, consequences, and etiology of drug abuse across individuals,
families, age groups, gender, communities, and population groups.

Mechanism of Support. This FOA
will utilize the NIH Exploratory/Developmental (R21) award mechanism and
runs in parallel with an FOA of identical scientific scope, PA-08-124, that
encourages applications under the R01 mechanism, and PA-08-126, that
encourages applications under the R03 mechanism.

Funds Available and Anticipated
Number of Awards. Awards issued under this FOA are contingent upon
the availability of funds and the submission of a sufficient number of
meritorious applications.

Budget and Project Period: The
total project period for an application submitted in response to this
funding opportunity may not exceed two years. Direct costs are limited to
$275,000 over an R21 two-year period, with no more than $200,000 in direct
costs allowed in any single year.

Research
Plan Component length: Item 3 of the Research
Plan of the R21 application may not exceed 6 pages, including tables, graphs, figures,
diagrams, and charts.

Eligible Project
Directors/Principal Investigators (PDs/PIs):Include Individuals with
the skills, knowledge, and resources necessary to carry out the proposed
research are invited to work with their institution/organization to
develop an application for support. Individuals from underrepresented
racial and ethnic groups as well as individuals with disabilities are
always encouraged to apply for NIH support.

Number of PDs/PIs. More than
one PD/PI, or multiple PDs/PIs, may be designated on the application..

Number of Applications. Applicants may submit
more than one application, provided that each application is
scientifically distinct.

Resubmissions.Applicants may submit a
resubmission application, but such application must include an Introduction
addressing the previous peer review critique (Summary Statement).

Renewals.Exploratory/developmental grant
support is for new projects only; competing renewal (formerly competing
continuation) applications will not be accepted.

Application
Materials.SeeSection IV.1for application materials.All applications, including resubmission, revision and renewal, submitted for due dates January 25, 2010 and beyond, must utilize the current forms and instructions.

General Information.For general
information on SF424 (R&R) Application and Electronic Submission, see these
Web sites:

This Funding Opportunity Announcement (FOA) issued by the
National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH),
supersedes PA-06-329 and is intended to
stimulate innovative investigations, based on the R21 mechanism, that enhance
our understanding of: (1) drug use patterns and trends within and across
populations; (2) interplay of social interactions, social environment,
structural context with individual behavioral characteristics and genetic
vulnerability; (3) the phenotypic heterogeneity of drug abuse; (4) causal
mechanisms leading to onset, maintenance, and remittance of drug abuse and HIV
risk behaviors, as well as protective mechanisms that reduce these risk
behaviors; (5) drug abuse over the life course, including developmental
processes that influence drug use and HIV risk trajectories and behavioral,
health, and social consequences of drug abuse and HIV; and (6) medical
consequences of drugs of abuse and co-occurring viral and bacterial infections
(e.g., HIV, HCV, TB, STIs and others). In addition, research is encouraged to
develop methodologies to improve the accuracy, efficiency, scope, timeliness,
and analytic yield of drug abuse epidemiologic data. Because of the breadth of
epidemiology research, applications are anticipated to reflect diverse and
multidisciplinary putative approaches and multiple levels of causation. To take
advantage of the strength of specific research fields in an efficient manner,
and to maximize the generalizability of findings, researchers are encouraged to
develop and/or incorporate innovations in epidemiologic study design. Such
designs may include nesting of biological and/or basic research, contextual
analysis, and contemporary longitudinal analyses.

Background

Drug abuse epidemiologic research focuses on
understanding the nature, extent, consequences, and etiology of drug abuse
across individuals, families, age groups, gender, communities, and population
groups. Epidemiologic research plays a critical public health role by providing
an estimate of the magnitude, impact, and risk of drug abuse and related
problems on a population, and by laying the foundation for developing
strategies to prevent drug abuse, plan and evaluate drug abuse services, and
suggest new areas for basic, clinical, and treatment research.

The natural history of drug use, abuse, and addiction can
be observed most validly in epidemiologic studies. The population-based
approach provides specific advantages over research relying on samples of
convenience, such as clinical samples, by reducing the potential for selection
bias in observed associations while enhancing generalizability. There are,
however, limitations to epidemiologic research. Large sample sizes can pose
difficulties in terms of time and cost to obtain intensive and detailed
measures, particularly over extended periods of time. The observational nature
of epidemiologic drug abuse research can limit experimental control and
manipulation of variables under study. However, underutilized applications in
epidemiologic study design, such as nested case control studies, enable
integration of focused intensive measurement in the context of epidemiologic
research. It is possible to draw epidemiologically informative samples, based
on specific characteristics, for recruitment into laboratory-based research.
Although collaboration between laboratory-based and epidemiologic research is
becoming more widespread in other areas of health research, it is less common
in the field of drug abuse research. This FOA encourages innovative research
that incorporates the strengths of epidemiologic and laboratory-based designs.

Recent advances in health science research have
recognized behavioral, social, psychosocial, biological, and genetic factors
across the spectrum of diseases, including drug abuse and addiction. For
diseases with a substantial environmental component, however, these as
individually or in combination, these factors are not sufficient to explain or
predict disease patterns. In order to better understand the epidemiology of
drug abuse and its consequences within and across populations, research is
encouraged on the interactive influence of environmental, social and cultural
factors, on the initiation and progression of drug use among population groups.
Novel conceptualization and measurement of environmental, social, and cultural
contexts within theoretically grounded research are important to the
advancement of drug abuse research. Ultimately, the successful identification
of specific genes and related biological/physiological systems and other
etiologic processes of complex diseases like addiction depend on precise,
quantitative measurements of personal environmental exposures to evaluate their
impact on disease risk. Increased understanding of how genetic, biological,
social, cultural and contextual phenomena interact to influence behavior will
inform prevention and treatment for individuals at risk for drug abuse and
addiction.

Crosscutting Issues

Research indicates that there are significant
gender-specific differences in biological factors in drug abuse and related risk
behaviors, antecedents and consequences of drug abuse, and responses to
prevention and treatment. Investigators should, wherever possible, include
adequate numbers of both male and female subjects in their studies in order to
make meaningful gender comparisons. Researchers are also encouraged to design
studies to explore gender differences in the nature and extent of drug-using
behaviors, including sexual risk behavior associated with injecting and
non-injecting drug abuse, in the pathways and determinants of initiation,
progression and maintenance of drug abuse, and the behavioral and social
consequences of drug abuse. For more information on research on this topic, see
the Women, Gender Differences and Drug Abuse: http://www.nida.nih.gov/WHGD/whgdpa.html#focus; http://grants.nih.gov/grants/guide/pa-files/PAR-06-476.html.
For additional information on these announcements, contact Cora Lee
Wetherington, Ph.D. at Wetherington@nih.gov.

HIV/AIDS and drug abuse are frequently referred to as
twin epidemics, and whenever possible, it is essential that epidemiologic
studies address this interrelationship. Investigators are encouraged to
incorporate appropriate measures and analyses of factors critical to
understanding transmission risks for HIV/AIDS and other sexually transmitted
diseases (STDs), Hepatitis (HCV and HCB), and Tuberculosis (TB), as well as
related disparities across different population groups. The aim is to promote
integrated approaches to understanding and addressing co-factors and
interactions among individuals and their environments that contribute to the
continuum of problems related to drug abuse, including HIV/AIDS. For more
information on research on this topic, see http://hiv.drugabuse.gov ; http://www.drugabuse.gov/MeetSum/HIVworkshop.html;
and www.nida.nih.gov/about/organization/arp/arp_pa&rfa.htm.

Research shows that minority groups, particularly Blacks
and Hispanics, are in some instances less likely to use licit or illicit drugs,
but that such groups tend to be over-represented among those who suffer from
co-occurring and adverse health, behavioral, and social consequences related to
drug use (e.g., HIV/AIDS, premature births, intentional and unintentional
injuries, violence, crime, unemployment and school dropout). Epidemiologic
research is clearly needed to inform prevention and intervention strategies
aimed at reducing and eliminating drug-related health disparities, as well as
services research on access, utilization, and retention of racial and ethnic
minority populations in drug abuse treatment. This announcement therefore
encourages research that focuses on identifying risk factors and consequences
that are unique to or more prevalent in subpopulations in socioeconomically
disadvantaged (i.e., low education level, poverty) and medically underserved
rural and urban communities. For more on NIDAs interest in this topic, see http://www.drugabuse.gov/StrategicPlan/HealthStratPlan.html.

Advances in the field of drug abuse epidemiology will
require innovations in statistical, epidemiologic, sociologic, and genetic
epidemiologic designs to meet challenges in the rapidly evolving drug abuse
field. As well, advancements in statistical and survey methods designed to
improve epidemiologic research, as well as data sharing and opportunities for
dissemination. These advancements include issues relating to diagnosis and
classification, such as refining diagnostic instruments and nomenclature. This
announcement encourages methodological innovations that address transitions in
stages and trajectories of drug abuse, intergenerational transmission of drug
abuse, and heterogeneous pathways to and consequences of drug abuse. Especially
encouraged are approaches that facilitate: (a) nested case-control and case-
cohort designs that efficiently combine the advantages of epidemiologic samples
with more intensive laboratory-based and biological measures, (b) innovations
in measurement such as real-time measures of drug abuse and associated risk
factors through the use of handheld devices, and (c) secondary analyses of
existing epidemiologic data sets that contain high-quality information about
drug abuse.

A great pubic investment
has been made in datasets that describe the risk factors, mediators,
moderators, course and progression of drug abuse and associated disorders.
While many important findings have emanated from these datasets, they remain
rich sources of data which can be further mined to advance the field.
Specifically, these datasets can be used for analyses to answer outstanding
questions in the field, to re-examine the data deploying new approaches based on
methodological and theoretical advances, and to undertake small projects that
will help identify appropriate directions for larger scale studies. For
instance, NIDA-funded genetic epidemiologic studies have generated a great deal
of strong, developmentally informed data, much of which remains to be analyzed,
using state-of-the-art approaches to existing data. Outstanding issues include
the conditionality of drug use disorders on drug exposure and methods of
combining data across studies to increase power. More work on nosology, causal
modeling, quantitative approaches, co-morbidity, phenotying, gender and ethnic
differences, and testing alternative models are merited. In addition, many
advances have been made in conceptualizing how the environment interacts with
individual factors over time to affect developmental outcomes. Taking
advantage of these advances, researchers have the opportunity to re-explore
datasets rich in environmental data to help pinpoint what features of the
environment are critical for drug addiction outcomes and at what points in time
relative to individual development.

For more information on research using secondary
analyses, particularly research on psychopathology vulnerability for drug
abuse, see PA-06-439,
Risk Factors for Psychopathology Using Existing Data. For more information
on research supporting development of measurement technologies, see the
Exposure Biology Program of the NIH Genes, Environment and Health Initiative
(GEI): http://www.gei.nih.gov/exposurebiology/index.asp.

Major Program Areas

The epidemiologic drug abuse research program is further
organized into major program areas that are described below. It is important to
note that the crosscutting issues of gender, HIV/AIDS, health disparities, and
methodological innovations apply across all of these topics. Examples of the
types of research topics include, but are not limited to, the following:

Emerging
and current trends in drug abuse and drug-related disorders

Social
epidemiology of drug abuse and drug-related problems

Genetic
liability and phenotypic heterogeneity

Drug abuse
and psychopathology: vulnerability and comorbidity

Human
development in adolescence and adulthood

Family
processes and early risks for drug use

Social and
behavioral consequences of street drugs

Drug
markets and behavior economics

Health and
medical consequences of drugs of abuse and co-occurring infections

Emerging and current trends in drug abuse and
drug-related disorders Research directed at examining drug abuse trends is
particularly important in the contemporary context where a variety of new
substances are available to increasingly diverse populations and in an
expanding range of settings. Changing availability and changing social and
cultural trends influence patterns of use. Research continues to reveal new
drug use trends and issues warranting further exploration such as the high level
of abuse of prescription drugs, patterns of use of drugs in combination, and
the association between non-injection drug use and HIV-risk behaviors in some
contexts. This program of research encourages: (a) studies that develop more
effective and timely ways to identify the nature, extent, and changes of new
trends at an early stage within local, national and international contexts, and
to identify associated health, social and behavioral consequences; (b)
theory-driven research models for understanding the diffusion of drug trends
into new populations including the impact of cultural factors, social networks,
drug distribution mechanisms and media; (c) exploratory descriptive
hypothesis-generating ethnographic studies as well as analytic studies that examine
factors impacting initiation, continuation, progression and cessation of use of
novel drugs; (d) studies that examine the relation between the use of novel
drugs and HIV-risk behaviors; (e) research into whether users of these new
substances experience substance use disorders; (f) innovative studies to
improve methods for characterizing drug use behaviors such as, for example, the
use of different substances strategically in combination or in sequence within
specified periods of time; and (g) studies on the impact of drug trends and
patterns on drug-related mortality.

Social epidemiology of drug abuse and drug-related
problems Drug abuse research has focused largely on individual risk factors,
while the universe of determinants includes individual, familial, neighborhood,
community, population-specific, and societal factors. There is urgent need to
extend drug abuse research to incorporate the concept of interactivity
(individual susceptibility interacting with social environment, genetic
environment, neighborhood environment) and cumulative history (how these
determinants differentially impose risk across time, generations, and the life
course). This program specifically encourages: (a) studies that examine the
interaction of individual and social environmental factors on drug
use/abuse/dependence; (b) studies that consider both immediate and cumulative
(life-course and trans- generational) effects of interactions among drug
abusing behaviors, environments, and genes; (c) studies that draw upon current
research on the effects of social environmental factors on health and disease
in general; (d) research that identifies whether and how the environment as
culture can be meaningfully disaggregated into measurable components and tested
for effects on drug abuse; (e) studies that inform the debate on which aspects
or dimensions of the social environment (e.g., society, social institution,
small group, dyad, social networks) also should be included, when they should
be included, and how they should be measured; (f) investigations of the
collective impact of neighborhood factors such as residential
stability/instability, collective efficacy, social cohesion or other aspects of
locally shared environments on drug abuse among different groups; (g) studies
of how social and cultural factors influence or predict drug use/abuse, drug
use related risk behavior, and its consequences; and (h) studies that
incorporate tools from geography and spatial epidemiology such as GIS and other
geomapping techniques to understand the interaction of environmental context
and drug use and abuse.

Genetic liability and phenotypic heterogeneity Numerous
genetic epidemiologic studies confirm that drug abuse "runs" in
families, and that such transmission is due in part to genetic factors. These
findings have been tremendously important, and have set the stage for
additional research to specify drug abuse phenotype(s) and
gene-by-environment-by development interactions inherent to complex disorders
such as drug abuse. Indeed, untangling the complicated pathways from genotypes
to phenotypes is one of the biggest challenges in the drug abuse field. The
objective of this program area is to further explicate the transmissibility of
drug abuse phenotypes as well as individual differences, familial processes,
and social/environmental factors that confer risk for or protect against the
expression of genetic liability. This program area encourages research on the
following topics: (a) the refinement of drug abuse phenotypes and nosology to
inform prevention, services, and molecular genetic research; (b) identification
of key individual and environmental characteristics that affect genetic
vulnerability and/or the course of drug abuse, including psychopathological
conditions; (c) the interplay among genetic, environmental, and developmental
factors (heritability, interactions, and correlations) for identifying and
fine-tuning preventive interventions with high-risk populations; (d) studies
that inform the debate on the general liability versus specificity of genetic
risk for drug abuse; (e) genetically- informative assessments that are nested
within epidemiologic-based studies; (f) development of statistical and analytic
approaches to model complex disorders and traits. Further details on the
genetic epidemiology program can be found at http://grants.nih.gov/grants/guide/pa-files/PA-07-413.html, http://grants.nih.gov/grants/guide/pa-files/PA-07-415.html,
and http://grants.nih.gov/grants/guide/pa-files/PA-07-414.html.

Drug abuse and psychopathology: vulnerability and
comorbidity Cross-sectional and longitudinal studies of adolescents and
adults in both clinical and general populations have found high rates of
co-occurrence between drug abuse and psychiatric disorders, particularly the
conduct/antisocial disorders and the mood disorders. Far fewer studies have
examined the temporal order or causal relationships, including potentially
common pathways, for specific psychiatric disorders and drug abuse. Thus, the
nature of the association among drug use disorders and other psychiatric
disorders remains unclear. Understanding the relations between precursor and
comorbid psychiatric disorders and drug abuse is a key focus of this program
and has important prevention and treatment implications. Specifically, this
program of research encourages studies that focus on: (a) child psychiatric
precursors to drug abuse, with a particular emphasis on attentional,
externalizing, and internalizing disorders; (b) the impact of mental health and
behavioral interventions on drug abuse risk; (c) moderating and mediating
factors that can inform the association between psychiatric disorders and drug
abuse; (e) temperament and personality, particularly behavioral disinhibition
and impulsivity, as stand-alone etiologic or potential mediating factors; and (f)
dynamic relations between the timing and course of psychiatric illness and the
timing and course of drug abuse, including drug use initiation, maintenance,
escalation, and remittance. Towards this end, research approaches of particular
interest to this program include: epidemiologic (population-based)
cross-sectional and longitudinal studies, genetic epidemiologic and other
studies of familial risk, clinical prospective and clinical follow-up studies,
innovative designs that characterize the interactions between individual
psychiatric and genetic factors with the environment, nested studies, and
secondary data analyses. For additional information related to psychopathology
and vulnerability for drug abuse, see http://www.drugabuse.gov/Meetings/Childhood.

Human development in adolescence and adulthood This
program focuses on three key adolescent developmental issues that have
relevance for drug abuse: timing, transitions, and biologic maturation. The
developmental stage when drugs are introduced has implications for drug abuse,
as evidenced by recent research showing that initiation during early
developmental periods is associated with greater subsequent use. Similarly,
developmental transitions (e.g., pubertal, cognitive, social, and achievement
related), and individual variation in the timing of these, are also likely to
influence trajectories of use. Studies of particular interest under this
program include, but are not limited to, those that assess: (a) how
developmental timing and the timing of drug use act and interact to influence
the course of drug using behavior and related outcomes; (b) the implications of
emerging cognitive, emotional, and social capacities across developmental
periods for drug abuse; (c) the impact of the adoption of stage-specific roles
on drug abuse and the impact of drug abuse on the adoption of such roles; (d)
the creation of new or implementation of existing methodologic approaches that
adequately capture the developmental nature of individual change; (e) real-time
assessment methodologies to capture the capricious and context-dependent nature
of drug using behaviors over developmental periods; and (f) translational
research including epidemiologic studies that incorporate lab-based findings on
adolescent brain development, measures of shifts in emotional and cognitive
processes, and assessments of biological changes associated with puberty.

Family processes and early risks for
drug use This program focuses on family processes and the consequences of
parental drug abuse as risk factors associated with youth drug abuse. Parent
drug abuse may influence childrens development through direct and indirect
pathways. Direct pathways include genetic transmission of vulnerability to
substance use disorders and prenatal exposure to drugs. Parent substance abuse
can also indirectly impact development through its effect on childrens
environments. Longitudinal, prospective, and multidisciplinary studies are
needed to investigate the independent and combined contributions of
biologic/genetic, psychosocial, and contextual factors that influence both drug
use and the development of children and adolescents. Youth populations at
heightened risk for drug abuse (e.g., homeless youth, youth in foster care) are
of particular interest. This program of research encourages studies that focus
on family processes, parent drug abuse, and risk behaviors (e.g., aggression,
self-regulation, coercive family interactions) as they relate to youth drug
abuse, as well as to early developmental processes linked with later drug use.
This program also encourages research focusing on other developmental outcomes
as well as the processes by which these factors influence child development.
Specifically, (a) independent and combined effects of family processes, parent
drug abuse, exposure to family and/or community violence and/or child
maltreatment; (b) effects of exposure to lifestyles associated with parent
involvement in illicit drug activities and related activities; (c) effects of
forced parent-child separations due to parental drug-related illness, death, or
imprisonment; (d) post-traumatic stress disorder (PTSD) as a risk factor for
youth drug use; (e) individual child characteristics, sociocultural risks,
contextual risks, and/or family dynamics that influence the development of
youth drug use and other developmental outcomes; and (f) family, peer, school,
and community influences on drug use/abuse.

Social and behavioral consequences of street drugs This
program focuses on the range of behavioral and social consequences arising from
street-level drug abuse. Behavioral consequences include educational and
occupational problems, crime and violence, and comorbid conditions (overdose,
suicide, trauma, abuse, STDs/HIV, and cognitive impairment). Social
consequences include drug trafficking and distribution, gang activities, family
disruption, and neighborhood dysfunction. Little attention has been given to
how abuse of particular drugs and combinations of drugs affects these
consequences. Understanding retail street drug activity and consumption
patterns are important to understanding drug distribution networks and drug
price/purity and availability. Data are available on the frequency of drug use,
but better estimates of drug price and purity, and a better understanding of
the quantity of drug used are sorely needed. Specifically, the street-level
drugs program encourages research on: (a) what, how much, and how often drugs
are actually consumed by drug users; (b) which adulterants, diluents, and
contaminants are present in retail drugs; (c) the patterns of use of different
drugs, including teasing apart patterns of polydrug use; and patterns of
injecting and non-injecting drug abuse, variations in those patterns, and
correlated risk behaviors associated with the acquisition and transmission of
HIV and other diseases; (d) economic analyses to understand issues such as
price/purity, consumption, and cross-elasticities; (e) small-scale
epidemiologic studies could characterize price, demand, and consequences at the
level of a city or other small geographic area; and (f) ethnographic studies to
describe price and availability effects on behavior of those who use, abuse, or
are dependent to explore whether elasticity of demand varies with severity of
drug use.

Drug markets and behavior economics Research
increasingly points to the importance of studying drug abuse as the behavior of
individuals in their environments. While the immediate (proximal) environments of
drug abusers have received considerable research attention, the context of
broader and more distal environmental influences have received less
consideration. Principles of behavior derived from more macro-environmental
disciplines, particularly economics, have great potential for expanding
understanding of the full set of influences on drug abuse. It is important to
examine the intersection of psychological, economic and environmental concepts
and findings and their relevance to drug abuse etiology, continuation, relapse
and hopefully, more effective preventive and treatment interventions. By
applying the research and perspectives of behavioral economics, marketing
research, drug availability market factors, the psychology of decision making
and other related areas, important but understudied pieces of the drug abuse
puzzle will be investigated. The following issues are of particular interest:
(a) nested case control studies within larger epidemiologic studies that enable
laboratory-based behavioral economic analysis of defined populations; (b)
research on the influence of environmental factors on behavioral economic
measures such as delayed discounting functions or impulsivity and risk taking;
and (c) interactions among broad social forces (e.g., neighborhood quality and
socioeconomic status), racial and ethnic health disparities, and drug abuse
trajectories and consequences.

Health and medical consequences of drugs of abuse and
co-occurring infections Research on the epidemiology and natural history of HIV/AIDS among drug
using populations includes studies of changing social and behavioral patterns
and trends in the epidemic of HIV/AIDS among drug users e.g., injection and
non-injection drug users and their sexual partners and risk, peer, and social networks.
As well, emphasis is place on understanding health outcomes and clinical
manifestations of HIV disease and co-morbid conditions in drug using
populations.

Topics of
interest to the Epidemiology Research Branch include, but are not limited to,
studies that characterize the risk factors and mechanisms of acquisition and
transmission of HIV and co-infections; multidisciplinary research on the
behavioral, cultural, social, and economic risk factors and HIV-related
consequences of drug abuse; research that advances qualitative and quantitative
methodologies in behavioral and social science investigations of drug abuse,
HIV/AIDS, and other infectious diseases; studies of individual or environmental
factors (including the neurobiological changes induced by acute or chronic
drugs of abuse) that affect HIV acquisition/transmission, disease progression,
or response to antiviral therapies; studies to identify and understand
potential cofactors, mediators, and interactions of HIV and other diseases,
their progression, and their outcomes in diverse groups (e.g., by HIV subtype,
by socio-demographic factors) of active drug users; and studies of new and
improved approaches to access and recruit hard-to-reach cohorts of active drug
users to participate in biomedical and behavioral interventions to reduce drug
use-related risk behaviors, disease transmission, and co-morbidity (e.g.,
sampling and survey methods, and strategies, including the use of the Internet,
to link community-based outreach to drug users with referral and access
programs for HIV counseling and testing services, diagnostic screening for
other diseases, drug treatment, and medical care). For these types of studies,
contact the Epidemiology Research Branch. For more on NIDAs interest in this
area, see also http://www.nida.nih.gov/about/organization/arp/arp-pa&rfa.htm and http://grants1.nih.gov/grants/guide/pa-files/PA-07-307.html.

The Medical
Consequences Branch in the Division of Pharmacotherapies and Medical
Consequences of Drug Abuse encourages basic and clinical studies to better
understand how HIV infection is established and maintained and the medical
consequences of HIV/AIDS in drug abusers. This research includes studies of
the role of drugs of abuse and related compounds (including adulterants and
contaminants of drugs of abuse) or drug abuse treatment medications on the
progression of HIV disease, antiretroviral-resistant HIV strains,
AIDS-associated opportunistic infections, and drug-associated mental health
disorders in drug users; of the medical/clinical consequences of drug use, HIV, and co-occurring
infections, which ranges across physiological and biochemical systems, e.g.,
metabolic/nutritional factors, that might impact the pathogenesis of HIV/AIDS;
physiological factors that affect resistance and susceptibility to infection,
e.g., effects of drug abuse on mucosal barriers, drug-drug interactions;
medical interventions for drug abuse, psychiatric illness, and HIV and
associated clinical conditions; interactions between drugs of abuse and
medications to treat drug abuse and pharmacotherapies for HIV/AIDS and comorbid
conditions; and pharmacological, physiological, genetic, and clinical factors
in the progression of infectious diseases in vulnerable and underserved
minority populations of drug users. For these types of studies, please refer to http://www.nida.nih.gov/about/organization/DPMCDA/mcb/MCBHome.html.Also
see http://www.nida.nih.gov/about/organization/arp/arp-pa&rfa.htm and http://grants1.nih.gov/grants/guide/pa-files/PA-07-307.html and contact Jag H. Khalsa, Ph.D., jk98p@nih.gov.

The evolution and
vitality of the biomedical sciences require a
constant infusion of new ideas, techniques, and points of view. These may
differ substantially from current thinking or practice and may not yet be
supported by substantial preliminary data. By using the R21 mechanism, the NIH seeks to foster the introduction of novel
scientific ideas, model systems, tools, agents, targets, and technologies that
have the potential to substantially advance biomedical research.

The R21 mechanism is intended to encourage new
exploratory and developmental research projects. For
example, such projects could assess the feasibility of a novel area of
investigation or a new experimental system that has the potential to enhance
health-related research. Another example could include the unique and innovative use of an existing methodology to explore
a new scientific area. These studies may involve considerable risk but may
lead to a breakthrough in a particular area, or to the development of novel
techniques, agents, methodologies, models, or applications
that could have a major impact on a field of biomedical, behavioral, or
clinical research.

Applications for R21 awards should describe
projects distinct from those supported through the traditional R01
mechanism. For example, long-term projects, or
projects designed to increase knowledge in a well-established area, will not be
considered for R21 awards. Applications submitted under this mechanism should
be exploratory and novel. These studies should break new ground or extend
previous discoveries toward new directions or
applications. Projects of limited cost or scope that use widely accepted
approaches and methods within well established fields are better suited for the
R03 small grant mechanism. Information on the R03 program can be found at http://grants.nih.gov/grants/funding/r03.htm.

Special
Considerations

HIV/AIDS
Counseling and Testing Policy for the National Institute on Drug Abuse: In light of recent significant
advances in rapid testing for HIV and in effective treatments for HIV, NIDA has
revised its 2001 policy on HIV counseling and testing. NIDA-funded researchers
are strongly encouraged to provide and/or refer research subjects to HIV risk
reduction education and education about the benefits of HIV treatment,
counseling and testing, referral to treatment, and other appropriate
interventions to prevent acquisition and transmission of HIV. This policy
applies to all NIDA funded research conducted domestically or internationally.
For more information see http://grants.nih.gov/grants/guide/notice-files/NOT-DA-07-013.html.

National Advisory
Council on Drug Abuse Recommended Guidelines for the Administration of Drugs to
Human Subjects: The National
Advisory Council on Drug Abuse (NACDA) recognizes the importance of research
involving the administration of drugs with abuse potential, and dependence or
addiction liability, to human subjects. Potential applicants are encouraged
to obtain and review these recommendations of Council before submitting an
application that will administer compounds to human subjects. The guidelines
are available on NIDA's Web site at http://www.nida.nih.gov/about/organization/nacda/CouncilStatement.html.

This
FOA will use the NIH
Exploratory/Developmental Research Grant (R21) award
mechanism. The Project Director/Principal
Investigator (PD/PI) will be solely responsible for planning, directing, and
executing the proposed project.

This FOA uses
Just-in-Time information concepts see SF424 (R&R) Application
Guide). It also uses the modular as well as
the non-modular budgetformats (see the Modular Applications and
Awards section of the NIH
Grants Policy Statement. Specifically, if you are submitting an
application with direct costs in each year of $250,000 or less (excluding
consortium Facilities and Administrative [F&A] costs), use the PHS398
Modular Budget component provided in the SF424 (R&R) Application Package
and SF424 (R&R) Application Guide (see specifically Section 3.4, Modular
Budget Component, of the Application Guide).

U.S. applicants requesting more than
$250,000 in annual direct costs and all Foreign applicants must complete and
submit budget requests using the Research & Related Budget component.

2. Funds Available

Because the nature and scope of the proposed
research will vary from application to application, it is anticipated that the
size and duration of each award will also vary. Although the financial plans of
the Institutes and Centers (ICs) provide support for this program, awards
pursuant to this funding opportunity are contingent upon the availability of
funds and the submission of a sufficient number of meritorious applications . The total project period for
an application submitted in response to this funding opportunity may not exceed
2 years. Although the size of award may vary with the scope of research
proposed, it is expected that applications will stay within the budgetary
guidelines for an exploratory/developmental project;
direct costs are limited to $275,000 over an R21 two-year period, with no more
than $200,000 in direct costs allowed in any single year. Applicants may
request direct costs in $25,000 modules, up to the total direct costs limitation of $275,000 for the combined two-year
award period. NIH grants policies as described in the NOT-OD-05-004, November 2, 2004.

Any
individual(s) with the skills, knowledge, and resources necessary to carry out
the proposed research as the PD/PI is invited to work with his/her organization
to develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

More
than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application
for projects that require a team science approach and therefore clearly do
not fit the single-PD/PI model. Additional
information on the implementation plans and policies and procedures to formally
allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi.All PDs/PIs must be registered in the NIH electronic
Research Administration (eRA) Commons prior to the
submission of the application (seehttp://era.nih.gov/ElectronicReceipt/preparing.htmfor instructions).

The
decision of whether to apply for a grant with a single PD/PI or multiple
PDs/PIs grant is the responsibility of the investigators and applicant
organizations and should be determined by the scientific goals of the project.
Applications for grants with multiple PDs/PIs will require additional
information, as outlined in the instructions below. When
considering the multiple PD/PI option, please be aware that the structure and
governance of the PD/PI leadership team as well as the knowledge, skills and
experience of the individual PDs/PIs will be factored into the assessment of
the overall scientific merit of the application. Multiple PDs/PIs on a project
share the authority and responsibility for leading and directing the project,
intellectually and logistically. Each PD/PI is responsible and accountable
to the grantee organization, or, as appropriate, to a collaborating
organization, for the proper conduct of the project or program, including the
submission of required reports. For further information on multiple PDs/PIs,
please seehttp://grants.nih.gov/grants/multi_pi.

Exploratory/developmental
grant support is for new projects only; competing renewal (formerly competing
continuation) applications will not be accepted.

Applicants may submit a resubmission, but such application must include an Introduction addressing
issues raised in the previous critique (Summary Statement).

Applicants may submit
more than one application, provided each application is scientifically
distinct.

Section IV. Application and Submission Information

To
download a SF424 (R&R) Application Package and SF424 (R&R) SBIR/STTR
Application Guide for completing the SF424 (R&R) forms for this FOA, use
the Apply for Grant Electronically button in this FOA or link to http://www.grants.gov/Apply/ and follow
the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

The
individual(s) designated as PDs/PIs on the application must be registered
also in the NIH eRA Commons. In the case of multiple PDs/PIs, all
PDs/PIs must be registered and be assigned the PI role in the eRA Commons prior to the submission of the application.

Each
PD/PI must hold a PD/PI account in the Commons. Applicants should not
share a Commons account for both an Authorized Organization
Representative/Signing Official (AOR/SO) role and a PD/PI role; however,
if they have both a PD/PI role and an NIH Internet Assisted Review (IAR)
role, both roles should exist under one Commons account.

When
multiple PDs/PIs are proposed, all PDs/PIs at the applicant organization
must be affiliated with that organization. PDs/PIs located at another
institution need not be affiliated with the applicant organization, but
must be affiliated with their own organization to be able to access the Commons.

This
registration/affiliation must be done by the AOR/SO or his/her designee
who is already registered in the Commons.

Both
the PD/PI and AOR/SO need separate accounts in the NIH eRA Commons since both
are authorized to view the application image.

Note that if a PD/PI is
also an NIH peer-reviewer with an Individual DUNS and CCR registration, that
particular DUNS number and CCR registration are for the individual reviewer
only. These are different than any DUNS number and CCR registration used by an
applicant organization. Individual DUNS and CCR registration should be used
only for the purposes of personal reimbursement and should not be used on any
grant applications submitted to the Federal Government.

Several of the steps of the
registration process could take four weeks or more. Therefore, applicants
should immediately check with their business official to determine whether
their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept
electronic applications only from organizations that have completed all
necessary registrations.

1. Request Application Information

Applicants must
download the SF424 (R&R) application forms and SF424 (R&R) Application
Guide for this FOA through Grants.gov/Apply.

Note:
Only the forms package directly attached to a specific FOA can be used. You
will not be able to use any other SF424 (R&R) forms (e.g., sample forms,
forms from another FOA), although some of the "Attachment" files may
be useable for more than one FOA.

Prepare all applications
using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide (MS
Word or PDF).

The SF424
(R&R) Application Guide is critical to submitting a complete and accurate
application to NIH. There are fields within the SF424 (R&R) application
components that, although not marked as mandatory, are required by NIH (e.g.,
the Credential log-in field of the Research & Related Senior/Key Person
Profile component must contain the PD/PIs assigned eRA Commons User ID).
Agency-specific instructions for such fields are clearly identified in the
Application Guide. For additional information, see Frequently Asked Questions
Application Guide,Electronic
Submission of Grant Applications.

The SF424 (R&R)
application is comprised of data arranged in separate components. Some
components are required, others are optional. The forms package associated with
this FOA in Grants.gov/APPLYwill
include all applicable components, required and optional. A completed application
in response to this FOA will include the following components:

Proposed research should provide special opportunities for furthering
research programs through the use of unusual talent, resources, populations, or
environmental conditions in other countries that are not readily available in
the United States (U.S.) or that augment existing
U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one
PD/PI to be designated as the "Contact PI, who will be responsible for
all communication between the PDs/PIs and the NIH, for assembling the
application materials outlined below, and for coordinating progress reports for
the project. The contact PD/PI must meet all eligibility requirements for PD/PI
status in the same way as other PDs/PIs, but has no other special roles or
responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in
Item 13 of the SF424 (R&R) Cover component. All other PDs/PIs should
be listed in the Research & Related Senior/Key Person component and
assigned the project role of PD/PI. Please remember that all PDs/PIs
must be registered in the eRA Commons prior to application submission. The Commons ID
of each PD/PI must be included in the Credential field of the Research &
Related Senior/Key Person component. Failure to include this data field
will cause the application to be rejected.

All
projects proposing Multiple PDs/PIs will be required to include a new section
describing the leadership plan approach for the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new
section of the research plan, entitled Multiple PD/PI Leadership Plan, must be
included. A rationale for choosing a multiple PD/PI approach should be
described. The governance and organizational structure of the leadership team
and the research project should be described, and should include communication
plans, process for making decisions on scientific direction, and procedures for
resolving conflicts. The roles and administrative, technical, and
scientific responsibilities for the project or program should be delineated for
the PDs/PIs and other collaborators.

If budget allocation
is planned, the distribution of resources to specific components of the project
or the individual PDs/PIs should be delineated in the Leadership Plan. In the
event of an award, the requested allocations may be reflected in a footnote on
the Notice of Award (NoA).

Applications Involving a Single Institution

When all PDs/PIs are within
a single institution, follow the instructions contained in the SF424 (R&R)
Application Guide.

Applications Involving Multiple Institutions

When multiple institutions
are involved, one institution must be designated as the prime institution and
funding for the other institution(s) must be requested via a subcontract to be
administered by the prime institution. When submitting a detailed budget, the
prime institution should submit its budget using the Research & Related
Budget component. All other institutions should have their individual
budgets attached separately to the Research & Related Subaward Budget
Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide
for further instruction regarding the use of the subaward budget form.

When submitting a modular
budget, the prime institution completes the PHS398 Modular Budget component
only. Information concerning the consortium/subcontract budget is provided
in the budget justification. Separate
budgets for each consortium/subcontract grantee are not required when using the
Modular budget format. See Section 3.4 of the Application Guide for further
instruction regarding the use of the PHS398 Modular Budget component.

To submit an application in
response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow
Steps 1-4. Note: Applications must only be submitted electronically.
PAPER APPLICATIONS WILL NOT BE ACCEPTED.3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully
received by Grants.gov no later than 5:00 p.m. local time (of the
applicant institution/organization) on the application due date(s). (See Section IV.3.A. for all dates.) If an application is not submitted
by the due date(s) and time, the application may be delayed in the review
process or not reviewed.

Once an application package has been successfully
submitted through Grants.gov, any errors have been addressed, and the assembled
application has been created in the eRA Commons, the PD/PI and the
Authorized Organization Representative/Signing Official (AOR/SO) have two
weekdays (Monday Friday, excluding Federal holidays) to view the application
image to determine if any further action is necessary.

If everything is acceptable, no
further action is necessary. The application will automatically
move forward to the Division of Receipt and Referral in the Center for
Scientific Review for processing after two weekdays, excluding Federal holidays.

Prior to the submission deadline, the
AOR/SO can Reject the assembled application and submit a
changed/corrected application within the two-day viewing window. This
option should be used if it is determined that some part of the
application was lost or did not transfer correctly during the submission
process, the AOR/SO will have the option to Reject the application and
submit a Changed/Corrected application. In
these cases, please contact the eRA Help Desk to ensure that the issues
are addressed and corrected. Once rejected, applicants should follow the
instructions for correcting errors in Section 2.12, including the
requirement for cover letters on late applications. The
Reject feature should also be used if you determine that warnings are
applicable to your application and need to be addressed now. Remember,
warnings do not stop further application processing. If an application
submission results in warnings (but no errors), it will automatically move
forward after two weekdays if no action is taken. Some warnings may
need to be addressed later in the process.

If
the two-day window falls after the submission deadline, the AOR/SO will have
the option to Reject the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or did not
transfer correctly during the submission process). The AOR/SO should first contact
the eRA Commons Helpdesk to
confirm the system error, document the issue, and determine the best course of
action. NIH will not penalize the applicant for an eRA Commons or Grants.gov
system issue.

If
the AOR/SO chooses to Reject the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH
late policy guidelines and may not be accepted. The reason for this delay
should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two days.

Upon
receipt, applications will be evaluated for completeness by the Center for
Scientific Review, NIH. Incomplete applications will not be reviewed.

There will
be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR/SO
receives the Grants.gov acknowledgments. The AOR/SO and the PI receive Commons
acknowledgments. Information related to the assignment of an application to a
Scientific Review Group is also in the Commons.

Note: Since email can be
unreliable, it is the responsibility of the applicant to check periodically on
their application status in the Commons.

The
NIH will not accept any application in response to this FOA that is essentially
the same as one currently pending initial merit review unless the applicant
withdraws the pending application. The NIH will not accept any application that
is essentially the same as one already reviewed. However, the NIH will accept a
resubmission application, but such application must include an Introduction
addressing the critique from the previous review.

All NIH
awards are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants
Policy Statement.

Pre-award costs are
allowable. A grantee may, at its own risk and without NIH prior approval, incur
obligations and expenditures to cover costs up to 90 days before the beginning
date of the initial budget period of a new award if such costs: are necessary
to conduct the project, and would be allowable under the grant, if awarded,
without NIH prior approval. If specific expenditures would otherwise require
prior approval, the grantee must obtain NIH approval before incurring the cost.
NIH prior approval is required for any costs to be incurred more than 90 days
before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project.
See the NIH
Grants Policy Statement. 6. Other Submission
Requirements

PD/PI Credential (e.g., Agency Login)

The
NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE
Project Director/Principal Investigator section, Credential log-in field of
the Research & Related Senior/Key Person Profile component. The applicant
organization must include its DUNS number in its Organization Profile in the
eRA Commons. This DUNS number must match the DUNS number provided at CCR
registration with Grants.gov. For additional information, see Registration
FAQs Important Tips -- Electronic Submission
of Grant Applications.

Organizational DUNS

The
applicant organization must include its DUNS number in its Organization Profile
in the eRA Commons. This DUNS number must match the DUNS number provided at CCR
registration with Grants.gov. For additional information, see Frequently Asked
Questions Application Guide, Electronic
Submission of Grant Applications.

PHS398 Research Plan Component Sections

While
each section of the Research Plan needs to be uploaded separately as
a PDF attachment, applicants are encouraged to construct the Research Plan
component as a single document, separating sections into distinct PDF
attachments just before uploading the files. This approach will enable
applicants to better monitor formatting requirements such as page limits. All
attachments must be provided to NIH in PDF format, filenames must be included
with no spaces or special characters, and a .pdf extension must be
used.

All application
instructions outlined in the SF424 (R&R) Application
Guide (MS
Word or PDF) are to be followed, incorporating "Just-in-Time" information
concepts, and with the following requirements for R21 applications:

R21
applications will use the modular as well as the non-modular budget formats and
"Just-in-Time" information concepts, with direct costs requested in
$25,000 modules, up to the total direct costs limitation of $275,000 over an
R21 two-year period. No more than $200,000 in direct costs will be allowed in
any single year. All Foreign applicants must complete and submit
budget requests using the Research & Related Budget component.

Item 3 of the Research Plan of the R21
application may not exceed 6
pages, including tables, graphs, figures, diagrams, and charts.

Introduction
(required for a resubmission application) is limited to one page.

Do not use the Appendix to circumvent the page limitations. An application that does not comply with the
required page limitations may be delayed in the review process.

Foreign Applications (Non-domestic (non-U.S.) Entity)

Indicate how the proposed project has specific relevance to
the mission and objectives of the IC and has the potential for significantly
advancing the health sciences in the United States.

Resource
Sharing Plan(s)

NIH
considers the sharing of unique research resources developed through
NIH-sponsored research an important means to enhance the value and further the
advancement of the research. When resources have been developed with NIH funds
and the associated research findings published or provided to NIH, it is
important that they be made readily available for research purposes to
qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this
must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

(a) Data Sharing Plan: Not Applicable

(b) Sharing Model Organisms: Regardless of
the amount requested, all applications where the development of model organisms
is anticipated are expectedto include a description of a
specific plan for sharing and distributing unique model organisms and related
resources, or state appropriate reasons why such sharing is restricted or not
possible. See Sharing
Model Organisms Policy, and NIH
Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount
requested, applicants seeking funding for a genome-wide association
study are expected to provide a plan for submission of GWAS data to the
NIH-designatedGWAS data repository, or provide an appropriate
explanation why submission to the repository is not possible. A
genome-wide association study is defined as any study of genetic variation
across the entire genome that is designed to identify genetic associations with
observable traits (e.g., blood pressure or weight) or the presence or absence
of a disease or condition. For further information see Policy for Sharing
of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies
(go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

The
adequacy of the resources sharing plan and any related data sharing plans will
be considered by Program staff of the funding organization when making
recommendations about funding applications. The effectiveness of the resource
sharing will be evaluated as part of the administrative review of each Non-Competing Grant
Progress Report (PHS 2590). See Section VI.3.,
Reporting.

Section V. Application Review Information

1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only
the review criteria described below will be considered in the review process.

2.
Review and Selection Process

Applications submitted for this funding opportunity
will be assigned to the ICs on the basis of established Public Health Service (PHS) referral guidelines.

Applications that are complete will be
evaluated for scientific and technical merit by (an) appropriate scientific
review group(s) in accordance with NIH peer review
procedures (http://grants1.nih.gov/grants/peer/) using the review criteria stated below.

As part of the initial merit review, all applications
will:

Undergo a selection process in which only those
applications deemed to have the highest scientific merit, generally the
top half of applications under review, will be discussed and assigned a
rating;

Receive a written critique; and

Receive a second
level of review by the appropriate national advisory council or board.

Applications
submitted in response to this funding opportunity will compete for available
funds with all other recommended applications submitted in response to this FOA.The following will be
considered in making funding decisions:

Scientific
and technical merit of the proposed project as determined by scientific
peer review.

Availability
of funds.

Relevance
of the proposed project to program priorities.

The NIH R21
exploratory/developmental grant is a mechanism for supporting novel scientific
ideas or new model systems, tools, or technologies that have the potential to
significantly advance our knowledge or the status of health-related
research.

Because the Research Strategy is limited to 6 pages, an exploratory/developmental grant
application need not have extensive background material or preliminary
information as one might normally expect in an R01 application.
Accordingly, reviewers will focus their evaluation on the conceptual framework,
the level of innovation, and the potential to significantly advance our
knowledge or understanding. Reviewers will place less emphasis on methodological
details and certain indicators traditionally used in evaluating the scientific
merit of R01 applications, including supportive preliminary data. Appropriate
justification for the proposed work can be provided through literature
citations, data from other sources, or, when available, from
investigator-generated data. Preliminary data are not required for R21
applications; however, they may be included if available.

The
goals of NIH supported research are to advance our understanding of biological
systems, to improve the control of disease, and to enhance health. In their
written critiques, reviewers will be asked to comment on each of the following
criteria in order to judge the likelihood that the proposed research will have
a substantial impact on the pursuit of these goals. Each of these criteria will
be addressed and considered in assigning the overall score, weighting them as
appropriate for each application.

Note that an application does not need to be strong in
all categories to be judged likely to have major scientific impact and thus
deserve a meritorious impact/priority score. For example, an investigator may propose
to carry out important work that by its nature is not innovative but is
essential to move a field forward.

Overall Impact. Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five core review criteria, and additional review criteria (as applicable for the project proposed).

Core Review Criteria. Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance: Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s): Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation: Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment: Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Additional Review Criteria

As applicable for the project
proposed, reviewers will consider the following additional items in the
determination of scientific and technical merit, but will not give separate
scores for these items.

Protections for Human Subjects. For
research that involves human subjects but does not involve one of the six
categories of research that are exempt under 45 CFR Part 46, the committee will
evaluate the justification for involvement of human subjects and the proposed
protections from research risk relating to their participation according to the
following five review criteria: 1) risk to subjects, 2) adequacy of protection
against risks, 3) potential benefits to the subjects and others, 4) importance
of the knowledge to be gained, and 5) data and safety monitoring for clinical
trials.

For research that involves human subjects and meets
the criteria for one or more of the six categories of research that are exempt
under 45 CFR Part 46, the committee will evaluate: 1) the justification for the
exemption, 2) human subjects involvement and characteristics, and 3) sources of
materials.

Inclusion of Women, Minorities, and Children.
When the proposed project involves clinical research, the committee will
evaluate the proposed plans for inclusion of minorities and members of both
genders, as well as the inclusion of children.

Vertebrate Animals. The committee
will evaluate the involvement of live vertebrate animals as part of the
scientific assessment according to the following five points: 1) proposed use of
the animals, and species, strains, ages, sex, and numbers to be used; 2)
justifications for the use of animals and for the appropriateness of the species
and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting
discomfort, distress, pain and injury to that which is unavoidable in the
conduct of scientifically sound research including the use of analgesic,
anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and
5) methods of euthanasia and reason for selection if not consistent with the
AVMA Guidelines on Euthanasia.

Resubmission Applications. When
reviewing a Resubmission application (formerly called an amended application),
the committee will evaluate the application as now presented, taking into
consideration the responses to comments from the previous scientific review
group and changes made to the project.

Renewal Applications. When reviewing
a Renewal application (formerly called a competing continuation application),
the committee will consider the progress made in the last funding period.

Revision Applications. When
reviewing a Revision application (formerly called a competing supplement
application), the committee will consider the appropriateness of the proposed
expansion of the scope of the project. If the Revision application relates to a
specific line of investigation presented in the original application that was
not recommended for approval by the committee, then the committee will consider
whether the responses to comments from the previous scientific review group are
adequate and whether substantial changes are clearly evident.

Biohazards. Reviewers will assess
whether materials or procedures proposed are potentially hazardous to research
personnel and/or the environment, and if needed, determine whether adequate
protection is proposed.

Additional Review Considerations

As applicable for the
project proposed, reviewers will address each of the following items, but will
not give scores for these items and should not consider them in providing an
overall impact score.

Budget and Period Support. Reviewers
will consider whether the budget and the requested period of support are fully
justified and reasonable in relation to the proposed research.

Select Agents Research. Reviewers
will assess the information provided in this section of the application,
including 1) the Select Agent(s) to be used in the proposed research, 2) the
registration status of all entities where Select Agent(s) will be used, 3) the
procedures that will be used to monitor possession use and transfer of Select
Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security
of the Select Agent(s).

Applications from Foreign Organizations.
Reviewers will assess whether the project presents special opportunities for
furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions that exist in other countries and
either are not readily available in the United States or augment existing U.S.
resources.

When relevant, reviewers will be instructed to comment
on the reasonableness of the following Resource Sharing Plans, or the rationale
for not sharing the following types of resources. However, reviewers will not
factor the proposed resource sharing plan(s) into the determination of
scientific merit or impact/priority score, unless noted otherwise in the FOA. Program
staff within the IC will be responsible for monitoring the resource sharing.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

Selection of an application for award is not an authorization
to begin performance. Any costs incurred before receipt of the NoA are at the
recipient's risk. These costs may be reimbursed only to the extent considered
allowable pre-award costs. See Section IV.5.,
Funding Restrictions.

A final
progress report, invention statement, and Financial Status Report are required
when an award is relinquished when a recipient changes institutions or when an
award is terminated.

Section
VII. Agency Contacts

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research (program), peer review, and financial or
grants management issues:

Human Subjects
Protection:Federal regulations (45 CFR 46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety
Monitoring Plan:Data and safety
monitoring is required for all types of clinical trials, including physiologic
toxicity and dose-finding studies (Phase I); efficacy studies (Phase II);
efficacy, effectiveness and comparative trials (Phase III). Monitoring should
be commensurate with risk. The establishment of data and safety monitoring
boards (DSMBs) is required for multi-site clinical trials involving
interventions that entail potential risks to the participants (NIH Policy for
Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing
Research Data:Investigators
submitting an NIH application seeking $500,000 or more in direct costs in any
single year are expected to include a plan for data sharing or state why this
is not possible (http://grants.nih.gov/grants/policy/data_sharing).Investigators should
seek guidance from their institutions, on issues related to institutional
policies and local institutional review board (IRB) rules, as well as local,
State and Federal laws and regulations, including the Privacy Rule. Reviewers
will consider the data sharing plan but will not factor the plan into the
determination of the scientific merit or the impact/priority score.

Policy for Genome-Wide
Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088.
For additional information, see http://grants.nih.gov/grants/gwas/.

Sharing of Model Organisms:NIH is committed to support efforts that encourage
sharing of important research resources including the sharing of model
organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh-Dole Act (see the NIH
Grants Policy Statement. Beginning October 1, 2004, all investigators
submitting an NIH application or contract proposal are expected to include in
the application/proposal a description of a specific plan for sharing and
distributing unique model organism research resources generated using NIH
funding or state why such sharing is restricted or not possible. This will
permit other researchers to benefit from the resources developed with public
funding. The inclusion of a model organism sharing plan is not subject to a
cost threshold in any year and is expected to be included in all applications
where the development of model organisms is anticipated.

Access to Research Data through the Freedom of
Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are: (1) first
produced in a project that is supported in whole or in part with Federal funds;
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Inclusion of Women, Minorities, and Children:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines
for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical
Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them.

Required Education on the Protection of Human Subject
Participants:NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy, investigators funded by the NIH
must submit or have submitted for them to the National Library of Medicines
PubMed Central (see http://www.pubmedcentral.nih.gov/), an electronic
version of their final, peer-reviewed manuscripts upon acceptance for publication,
to be made publicly available no later than 12 months after the official date
of publication. The NIH Public Access Policy is available at (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html).For more information, see the Public
Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable
Health Information:The Department
of Health and Human Services (HHS) issued final modification to the
"Standards for Privacy of Individually Identifiable Health
Information", the "Privacy Rule", on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance Portability and
Accountability Act (HIPAA) of 1996 that governs the protection of individually
identifiable health information, and is administered and enforced by the HHS
Office for Civil Rights (OCR).

Decisions about
applicability and implementation of the Privacy Rule reside with the researcher
and his/her institution. The OCR website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs
in NIH Grant Applications or Appendices:All applications and proposals for NIH funding
must be self-contained within specified page limitations. For publications
listed in the appendix and/or Progress report, Internet addresses (URLs) or
PubMed Central (PMC) submission identification numbers must be used for
publicly accessible on-line journal articles. Publicly accessible on-line
journal articles or PMC articles/manuscripts accepted for publication that are
directly relevant to the project may be included only as URLs or PMC
submission identification numbers accompanying the full reference in either
the Bibliography & References Cited section, the Progress Report
Publication List section, or the Biographical Sketch section of the NIH grant
application. A URL or PMC submission identification number citation may be
repeated in each of these sections as appropriate. There is no limit to the
number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:The Public
Health Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This FOA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.

Authority and
Regulations:This program is described in the Catalog of Federal
Domestic Assistance at http://www.cfda.gov/ and is not subject to
the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under
the authorization of Sections 301 and 405 of the Public Health Service Act as
amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and
45 CFR Parts 74 and 92. All awards are subject to the
terms and conditions, cost principles, and other considerations described in
the NIH
Grants Policy Statement.

The PHS strongly
encourages all grant recipients to provide a smoke-free workplace and
discourage the use of all tobacco products. In addition, Public Law 103-227,
the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in
some cases, any portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development services are
provided to children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

Loan Repayment
Programs:NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical,
pediatric, contraception, infertility, and health disparities related areas.
The LRP is an important component of NIH's efforts to recruit and retain the
next generation of researchers by providing the means for developing a research
career unfettered by the burden of student loan debt. Note that an NIH grant is
not required for eligibility and concurrent career award and LRP applications
are encouraged. The periods of career award and LRP award may overlap providing
the LRP recipient with the required commitment of time and effort, as LRP
awardees must commit at least 50% of their time (at least 20 hours per week
based on a 40 hour week) for two years to the research. For further
information, please see: http://www.lrp.nih.gov/.